Zhang Lan, Xiong Xi, Lu Weiwen, Li Jiazheng, Zhang Ruotong, Cai Zhipeng, Lv Huixia, Zhang Zhenhai, Ju Jianming, Yang Ye
School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
Drug Deliv Transl Res. 2025 Aug 29. doi: 10.1007/s13346-025-01918-5.
Ulcerative colitis (UC), an inflammatory bowel disease, poses a severe threat to human health. Paeonol has demonstrated potential for the treatment of UC, particularly because of its remarkable anti-inflammatory properties. However, the high volatility and low oral bioavailability of paeonol hinder its application in the treatment of UC. To address this challenge, a paeonol emulsion (PEM)-based oral delivery system was developed for the treatment of UC. In this study, we investigated the colonic-targeting efficacy of PEM and the mechanisms underlying its ability to alleviate colitis. The results revealed that the negatively charged PEM specifically adhered to the positively charged inflamed colonic tissues via electrostatic interactions, enabling effective targeted delivery. Additionally, the PEM maintained the balance between M1 and M2 macrophages, exhibiting excellent efficacy in alleviating UC. Mechanistic studies have shown that PEM significantly inhibits the expression of inflammatory cytokines and repairs the intestinal barrier. Furthermore, PEM modulates the composition of the gut microbiota by inhibiting the growth of harmful bacteria and promoting the growth of beneficial bacteria. In conclusion, the negatively charged emulsion delivery system constructed provides new insights into the development of an oral colon-targeted drug delivery system.
溃疡性结肠炎（UC）是一种炎症性肠病，对人类健康构成严重威胁。丹皮酚已显示出治疗UC的潜力，特别是因其具有显著的抗炎特性。然而，丹皮酚的高挥发性和低口服生物利用度阻碍了其在UC治疗中的应用。为应对这一挑战，开发了一种基于丹皮酚乳液（PEM）的口服给药系统用于治疗UC。在本研究中，我们研究了PEM的结肠靶向疗效及其缓解结肠炎能力的潜在机制。结果表明，带负电荷的PEM通过静电相互作用特异性地粘附于带正电荷的炎症结肠组织，实现了有效的靶向递送。此外，PEM维持了M1和M2巨噬细胞之间的平衡，在缓解UC方面表现出优异的疗效。机制研究表明，PEM显著抑制炎症细胞因子的表达并修复肠道屏障。此外，PEM通过抑制有害细菌的生长和促进有益细菌的生长来调节肠道微生物群的组成。总之，构建的带负电荷的乳液递送系统为口服结肠靶向给药系统的开发提供了新的见解。
